Schizophrenia is a severely debilitating psychiatric disorder that afflicts approximately 1% of the population and is a serious public health problem with no cure. Cognitive deficits are a core feature of the illness with learning and memory deficits being particularly disabling. Patients with severe learning and memory impairments have poorer psychosocial function and life quality. Unfortunately, there are no good treatments for learning and memory impairments in schizophrenia. Consequently, there is a need for a better understanding of the neurobiological mechanisms of learning and memory failure and success in schizophrenia. These mechanisms are potential targets for novel treatment development. The proposed study will use multimodal neuroimaging methods to investigate relational learning in schizophrenia. Functional magnetic resonance imaging (fMRI) will be used to investigate neural activation during relational learning in schizophrenia. Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H-MRS) will be used to help determine whether altered neural activation patterns in schizophrenia are related to compromised structural white matter connections or neurochemistry. The neurobiological mechanisms related to the heterogeneity of learning performance in schizophrenia will be characterized. The third aim is to examine if altered neurobiology associated with relational learning in schizophrenia has a genetic influence by examining first-degree relatives. This will be the first study to use three neuroimaging techniques to investigate relational learning in schizophrenia. The combination of these techniques is expected to provide a more comprehensive picture of altered neurobiological mechanisms associated with relational learning in schizophrenia than any one technique alone. PUBLIC HEALTH RELEVANCE: Schizophrenia is a severely debilitating psychiatric disorder that afflicts approximately 1% of the population and is a serious public health problem. There are no good treatments for learning and memory deficits, core features of the disorder that negatively impact quality of life. This study will use three neuroimaging techniques to investigate neural activation patterns, white matter circuitry, and neurochemistry associated with relational learning in schizophrenia. It is predicted that the integration of these measurements will serve as targets for the development of novel drug and behavioral treatment for learning and memory deficits in schizophrenia.